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Koichi Otani - One of the best experts on this subject based on the ideXlab platform.
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single oral dose pharmacokinetics of Quazepam is influenced by cyp2c19 activity
Therapeutic Drug Monitoring, 2004Co-Authors: Takashi Fukasawa, Norio Yasuifurukori, Toshiaki Aoshima, Akihito Suzuki, Tomonori Tateishi, Koichi OtaniAbstract:The effects of cytochrome P450 (CYP)2C19 activity and cigarette smoking on the single oral dose pharmacokinetics of Quazepam were studied in 20 healthy Japanese volunteers. Twelve subjects were extensive metabolizers (EMs), and 8 subjects were poor metabolizers (PMs) by CYP2C19 as determined by the PCR-based genotyping. Nine subjects were smokers (>10 cigarettes/d), and 11 subjects were nonsmokers. The subjects received a single oral 20-mg dose of Quazepam, and blood samplings and evaluation of psychomotor function were conducted up to 72 hours after dosing. Plasma concentrations of Quazepam and its active metabolite 2-oxoQuazepam (OQ) were measured by HPLC. There were significant differences between EMs and PMs in the peak plasma concentration (mean +/- SD: 34.5 +/- 16.6 versus 66.2 +/- 19.2 ng/mL, P < 0.01) and total area under the plasma concentration-time curve (490.1 +/- 277.5 vs 812.1 +/- 267.2 ng x h/mL, P < 0.05) of Quazepam. The pharmacokinetic parameters of OQ and pharmacodynamic parameters were not different between the 2 groups. Smoking status did not affect the pharmacokinetic parameters of Quazepam and OQ or pharmacodynamic parameters. The present study suggests that the single oral dose pharmacokinetics of Quazepam are influenced by CYP2C19 activity but not by cigarette smoking.
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interaction study between fluvoxamine and Quazepam
The Journal of Clinical Pharmacology, 2003Co-Authors: Hideto Kanda, Norio Yasuifurukori, Takashi Fukasawa, Toshiaki Aoshima, Akihito Suzuki, Koichi OtaniAbstract:It has been reported that fluvoxamine, an inhibitor of various cytochrome P450 enzymes, markedly inhibits the metabolism of several drugs. The purpose of the present study was to examine a possible interaction between fluvoxamine and Quazepam. Twelve healthy male volunteers received fluvoxamine 50 mg/day or placebo for 14 days in a double-blind randomized crossover manner, and on the 4th day they received a single oral 20-mg dose of Quazepam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 240 hours after Quazepam dosing. Plasma concentrations of Quazepam and its active metabolites 2-oxoQuazepam (OQ) and N-desalkyl-2-oxoQuazepam (DOQ) were measured by high-performance liquid chromatography (HPLC). Fluvoxamine did not change plasma concentrations of Quazepam but significantly decreased those of OQ from 6 to 12 hours and those of DOQ from 3 to 48 hours. The AUC ratio of OQ to Quazepam was significantly lower in the fluvoxamine phase. Fluvoxamine did not affect psychomotor function at most of the time points. The present study suggests that fluvoxamine slightly inhibits the metabolism of Quazepam to OQ, but this interaction appears to have minimal clinical significance.
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effects of itraconazole on the plasma kinetics of Quazepam and its two active metabolites after a single oral dose of the drug
Therapeutic Drug Monitoring, 2003Co-Authors: Kimiyasu Kato, Norio Yasuifurukori, Takashi Fukasawa, Toshiaki Aoshima, Akihito Suzuki, Muneaki Kanno, Koichi OtaniAbstract:The effects of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the plasma kinetics of Quazepam and its two active metabolites after a single oral dose of the drug were studied. Ten healthy male volunteers received itraconazole 100 mg/d or placebo for 14 days in a double-blind randomized crossover manner, and on the fourth day of the treatment they received a single oral 20-mg dose of Quazepam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 240 h after Quazepam dosing. Itraconazole treatment did not change the plasma kinetics of Quazepam but significantly decreased the peak plasma concentration and area under the plasma concentration-time curve of 2-oxoQuazepam and N-desalkyl-2-oxoQuazepam. Itraconazole treatment did not affect either of the psychomotor function parameters. The present study thus suggests that CYP 3A4 is partly involved in the metabolism of Quazepam.
Norio Yasuifurukori - One of the best experts on this subject based on the ideXlab platform.
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single oral dose pharmacokinetics of Quazepam is influenced by cyp2c19 activity
Therapeutic Drug Monitoring, 2004Co-Authors: Takashi Fukasawa, Norio Yasuifurukori, Toshiaki Aoshima, Akihito Suzuki, Tomonori Tateishi, Koichi OtaniAbstract:The effects of cytochrome P450 (CYP)2C19 activity and cigarette smoking on the single oral dose pharmacokinetics of Quazepam were studied in 20 healthy Japanese volunteers. Twelve subjects were extensive metabolizers (EMs), and 8 subjects were poor metabolizers (PMs) by CYP2C19 as determined by the PCR-based genotyping. Nine subjects were smokers (>10 cigarettes/d), and 11 subjects were nonsmokers. The subjects received a single oral 20-mg dose of Quazepam, and blood samplings and evaluation of psychomotor function were conducted up to 72 hours after dosing. Plasma concentrations of Quazepam and its active metabolite 2-oxoQuazepam (OQ) were measured by HPLC. There were significant differences between EMs and PMs in the peak plasma concentration (mean +/- SD: 34.5 +/- 16.6 versus 66.2 +/- 19.2 ng/mL, P < 0.01) and total area under the plasma concentration-time curve (490.1 +/- 277.5 vs 812.1 +/- 267.2 ng x h/mL, P < 0.05) of Quazepam. The pharmacokinetic parameters of OQ and pharmacodynamic parameters were not different between the 2 groups. Smoking status did not affect the pharmacokinetic parameters of Quazepam and OQ or pharmacodynamic parameters. The present study suggests that the single oral dose pharmacokinetics of Quazepam are influenced by CYP2C19 activity but not by cigarette smoking.
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interaction study between fluvoxamine and Quazepam
The Journal of Clinical Pharmacology, 2003Co-Authors: Hideto Kanda, Norio Yasuifurukori, Takashi Fukasawa, Toshiaki Aoshima, Akihito Suzuki, Koichi OtaniAbstract:It has been reported that fluvoxamine, an inhibitor of various cytochrome P450 enzymes, markedly inhibits the metabolism of several drugs. The purpose of the present study was to examine a possible interaction between fluvoxamine and Quazepam. Twelve healthy male volunteers received fluvoxamine 50 mg/day or placebo for 14 days in a double-blind randomized crossover manner, and on the 4th day they received a single oral 20-mg dose of Quazepam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 240 hours after Quazepam dosing. Plasma concentrations of Quazepam and its active metabolites 2-oxoQuazepam (OQ) and N-desalkyl-2-oxoQuazepam (DOQ) were measured by high-performance liquid chromatography (HPLC). Fluvoxamine did not change plasma concentrations of Quazepam but significantly decreased those of OQ from 6 to 12 hours and those of DOQ from 3 to 48 hours. The AUC ratio of OQ to Quazepam was significantly lower in the fluvoxamine phase. Fluvoxamine did not affect psychomotor function at most of the time points. The present study suggests that fluvoxamine slightly inhibits the metabolism of Quazepam to OQ, but this interaction appears to have minimal clinical significance.
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effects of itraconazole on the plasma kinetics of Quazepam and its two active metabolites after a single oral dose of the drug
Therapeutic Drug Monitoring, 2003Co-Authors: Kimiyasu Kato, Norio Yasuifurukori, Takashi Fukasawa, Toshiaki Aoshima, Akihito Suzuki, Muneaki Kanno, Koichi OtaniAbstract:The effects of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the plasma kinetics of Quazepam and its two active metabolites after a single oral dose of the drug were studied. Ten healthy male volunteers received itraconazole 100 mg/d or placebo for 14 days in a double-blind randomized crossover manner, and on the fourth day of the treatment they received a single oral 20-mg dose of Quazepam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 240 h after Quazepam dosing. Itraconazole treatment did not change the plasma kinetics of Quazepam but significantly decreased the peak plasma concentration and area under the plasma concentration-time curve of 2-oxoQuazepam and N-desalkyl-2-oxoQuazepam. Itraconazole treatment did not affect either of the psychomotor function parameters. The present study thus suggests that CYP 3A4 is partly involved in the metabolism of Quazepam.
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time effects of food intake on the pharmacokinetics and pharmacodynamics of Quazepam
British Journal of Clinical Pharmacology, 2003Co-Authors: Norio Yasuifurukori, Tsuyoshi Kondo, Takenori Takahata, Kazuo Mihara, Sunao Kaneko, Tomonori TateishiAbstract:Aims There is little information on interaction between food and the hypnotic agent Quazepam. We therefore studied the effects of food and its time interval on the pharmacokinetics and pharmacodynamics of Quazepam. Methods A randomized three-phase crossover study with 2-week intervals was conducted. Nine healthy male volunteers took a single oral 20 mg dose of Quazepam under the following conditions: 1) after fasting overnight; 2) 30 min after eating standard meal; or 3) 3 h after eating the same meal. Plasma concentrations of Quazepam and its metabolite, 2-oxoQuazepam and psychomotor function using the Digit Symbol Substitute Test (DSST), Stanford Sleepiness Scale (SSS) and Visual Analogue Scale were measured up to 48 h. Results During the food treatments at 30 min and 3 h before dosing, the peak concentrations (Cmax) were 300% (95% CI 260, 340%; P < 0.001) and 250% (95% CI 210, 290%; P < 0.01) of the corresponding value during the fasting phase. For Quazepam, the area under the plasma concentration–time curve from 0 to 8 h measured at 30 min and 3 h before dosing was significantly increased, with the food treatments by 2.4-fold (95% CI 2.0; 2.8-fold; P < 0.001) and 2.1-fold (95% CI 1.7; 2.4-fold; P < 0.01), respectively. In response to pharmacokinetic changes, some of the pharmacodynamics (DSST, P < 0.05; SSS, P < 0.05) differed significantly between fasted status and fed status. No difference was found in any pharmacokinetic or pharmacodynamic parameters between the two food treatment phases. Conclusions A food effect on Quazepam absorption is evident and continues at least until 3 h after food intake. The dosing of Quazepam after a long period of ordinary fasting might reduce its efficacy because a 3 h interval between the timing of the evening meal and bedtime administration of hypnotics is regarded as normal in daily life.
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effect of dietary fat content in meals on pharmacokinetics of Quazepam
The Journal of Clinical Pharmacology, 2002Co-Authors: Norio Yasuifurukori, Tsuyoshi Kondo, Takenori Takahata, Kazuo Mihara, Shingo Ono, Sunao Kaneko, Tomonori TateishiAbstract:Dietary fat content in meals has been reported to increase the absorption of several drugs proportionately. However, there is no information about the effects of dietary fat in meals on the sedative hypnotic agent Quazepam, although limited data suggest that food intake alters Quazepam absorption. Therefore, the authors measured and compared pharmacokinetic parameters of Quazepam taken in a fasted state and taken 30 minutes after consuming meals containing different amounts of dietary fat. A three-arm randomized crossover study was conducted. Nine healthy male volunteers took a single oral 20-mg dose of Quazepam under the following conditions: (1) after fasting overnight for at least 12 hours, (2) 30 minutes after consuming a low-fat meal (two slices of bread and 200 ml of apple juice), or (3) 30 minutes after consuming high-fat meal (two slices of bread with 30 gm of butter and 200 ml of apple juice). Plasma concentrations of Quazepam and its metabolite, 2-oxoQuazepam, were monitored up to 48 hours after the dosing. In comparison with corresponding plasma values for Quazepam taken in a fasting state, the peak concentrations (C max ) of Quazepam taken 30 minutes after consuming a low-fat meal and high-fat meal were 243% (90% confidence interval [CI] = 161%-325%) and 272% (90% CI = 190%-355%), respectively. Area under the plasma concentration-time curve from 0 to 8 hours (AUC 0-8 ) and 0 to 48 hours (AUC 0-48 ) of Quazepam was increased with the low-fat meal by 2-fold (90% CI= 1.5- to 2. 7-fold) and 1.4-fold (90% CI = 1.0- to 1. 7-fold), respectively, and with the high-fat meal by 2.2-fold (90% CI= 1.3- to 3-fold) and 1.5-fold (90% CI= 0. 7- to 2.4-fold), respectively. The pharmacokinetic change in 2-oxoQuazepam to the parent compound was similar. Quazepam was well tolerated, with no significant difference in the Stanford Sleepiness Scale between fasted and fed conditions. These findings show that food intake has an evident effect on Quazepam absorption, but further studies are needed to clarify a determinant factor of this alternation (2.5-fold for C max and 2.1-fold for AUC 0-8 , on average). It might not be necessary to do dose adjustment with meal content because Quazepam is well tolerated.
Takashi Fukasawa - One of the best experts on this subject based on the ideXlab platform.
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single oral dose pharmacokinetics of Quazepam is influenced by cyp2c19 activity
Therapeutic Drug Monitoring, 2004Co-Authors: Takashi Fukasawa, Norio Yasuifurukori, Toshiaki Aoshima, Akihito Suzuki, Tomonori Tateishi, Koichi OtaniAbstract:The effects of cytochrome P450 (CYP)2C19 activity and cigarette smoking on the single oral dose pharmacokinetics of Quazepam were studied in 20 healthy Japanese volunteers. Twelve subjects were extensive metabolizers (EMs), and 8 subjects were poor metabolizers (PMs) by CYP2C19 as determined by the PCR-based genotyping. Nine subjects were smokers (>10 cigarettes/d), and 11 subjects were nonsmokers. The subjects received a single oral 20-mg dose of Quazepam, and blood samplings and evaluation of psychomotor function were conducted up to 72 hours after dosing. Plasma concentrations of Quazepam and its active metabolite 2-oxoQuazepam (OQ) were measured by HPLC. There were significant differences between EMs and PMs in the peak plasma concentration (mean +/- SD: 34.5 +/- 16.6 versus 66.2 +/- 19.2 ng/mL, P < 0.01) and total area under the plasma concentration-time curve (490.1 +/- 277.5 vs 812.1 +/- 267.2 ng x h/mL, P < 0.05) of Quazepam. The pharmacokinetic parameters of OQ and pharmacodynamic parameters were not different between the 2 groups. Smoking status did not affect the pharmacokinetic parameters of Quazepam and OQ or pharmacodynamic parameters. The present study suggests that the single oral dose pharmacokinetics of Quazepam are influenced by CYP2C19 activity but not by cigarette smoking.
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interaction study between fluvoxamine and Quazepam
The Journal of Clinical Pharmacology, 2003Co-Authors: Hideto Kanda, Norio Yasuifurukori, Takashi Fukasawa, Toshiaki Aoshima, Akihito Suzuki, Koichi OtaniAbstract:It has been reported that fluvoxamine, an inhibitor of various cytochrome P450 enzymes, markedly inhibits the metabolism of several drugs. The purpose of the present study was to examine a possible interaction between fluvoxamine and Quazepam. Twelve healthy male volunteers received fluvoxamine 50 mg/day or placebo for 14 days in a double-blind randomized crossover manner, and on the 4th day they received a single oral 20-mg dose of Quazepam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 240 hours after Quazepam dosing. Plasma concentrations of Quazepam and its active metabolites 2-oxoQuazepam (OQ) and N-desalkyl-2-oxoQuazepam (DOQ) were measured by high-performance liquid chromatography (HPLC). Fluvoxamine did not change plasma concentrations of Quazepam but significantly decreased those of OQ from 6 to 12 hours and those of DOQ from 3 to 48 hours. The AUC ratio of OQ to Quazepam was significantly lower in the fluvoxamine phase. Fluvoxamine did not affect psychomotor function at most of the time points. The present study suggests that fluvoxamine slightly inhibits the metabolism of Quazepam to OQ, but this interaction appears to have minimal clinical significance.
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effects of itraconazole on the plasma kinetics of Quazepam and its two active metabolites after a single oral dose of the drug
Therapeutic Drug Monitoring, 2003Co-Authors: Kimiyasu Kato, Norio Yasuifurukori, Takashi Fukasawa, Toshiaki Aoshima, Akihito Suzuki, Muneaki Kanno, Koichi OtaniAbstract:The effects of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the plasma kinetics of Quazepam and its two active metabolites after a single oral dose of the drug were studied. Ten healthy male volunteers received itraconazole 100 mg/d or placebo for 14 days in a double-blind randomized crossover manner, and on the fourth day of the treatment they received a single oral 20-mg dose of Quazepam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 240 h after Quazepam dosing. Itraconazole treatment did not change the plasma kinetics of Quazepam but significantly decreased the peak plasma concentration and area under the plasma concentration-time curve of 2-oxoQuazepam and N-desalkyl-2-oxoQuazepam. Itraconazole treatment did not affect either of the psychomotor function parameters. The present study thus suggests that CYP 3A4 is partly involved in the metabolism of Quazepam.
Akio Fujimura - One of the best experts on this subject based on the ideXlab platform.
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Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam and Quazepam
European Journal of Clinical Pharmacology, 2006Co-Authors: Koh-ichi Sugimoto, Masami Ohmori, Atsuhiro Kawaguchi, Shuichi Tsuruoka, N. Araki, Kenichi Harada, Y Cui, Akio FujimuraAbstract:Objective: Grapefruit juice (GFJ) inhibits cytochrome P450 (CYP) 3A4 in the gut wall and increases blood concentrations of CYP3A4 substrates by the enhancement of oral bioavailability. The effects of GFJ on two benzodiazepine hypnotics, triazolam (metabolized by CYP3A4) and Quazepam (metabolized by CYP3A4 and CYP2C9), were determined in this study. Methods: The study consisted of four separate trials in which nine healthy subjects were administered 0.25 mg triazolam or 15 mg Quazepam, with or without GFJ. Each trial was performed using an open, randomized, cross-over design with an interval of more than 2 weeks between trials. Blood samples were obtained during the 24-h period immediately following the administration of each dose. Pharmacodynamic effects were determined by the digit symbol substitution test (DSST) and utilizing a visual analog scale. Results GFJ increased the plasma concentrations of both triazolam and Quazepam and of the active metabolite of Quazepam, 2-oxoQuazepam. The area under the curve (AUC)(0–24) of triazolam significantly increased by 96% ( p
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interaction between grapefruit juice and hypnotic drugs comparison of triazolam and Quazepam
European Journal of Clinical Pharmacology, 2006Co-Authors: Koh-ichi Sugimoto, Masami Ohmori, Atsuhiro Kawaguchi, Shuichi Tsuruoka, N. Araki, Kenichi Harada, Y Cui, Akio FujimuraAbstract:Objective: Grapefruit juice (GFJ) inhibits cytochrome P450 (CYP) 3A4 in the gut wall and increases blood concentrations of CYP3A4 substrates by the enhancement of oral bioavailability. The effects of GFJ on two benzodiazepine hypnotics, triazolam (metabolized by CYP3A4) and Quazepam (metabolized by CYP3A4 and CYP2C9), were determined in this study.
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drug interaction between st john s wort and Quazepam
British Journal of Clinical Pharmacology, 2004Co-Authors: Atsuhiro Kawaguchi, Masami Ohmori, Shuichi Tsuruoka, Kenta Nishiki, Kenichi Harada, Isamu Miyamori, Ryoichi Yano, Toshiaki Nakamura, Mikio Masada, Akio FujimuraAbstract:Aim St John's Wort (SJW) enhances CYP3A4 activity and decreases blood concentrations of CYP3A4 substrates. In this study, the effects of SJW on a benzodiazepine hypnotic, Quazepam, which is metabolized by CYP3A4, were examined. Methods Thirteen healthy subjects took a single dose of Quazepam 15 mg after treatment with SJW (900 mg day−1) or placebo for 14 days. The study was performed in a randomized, placebo-controlled, cross-over design with an interval of 4 weeks between the two treatments. Blood samples were obtained during a 48 h period and urine was collected for 24 h after each dose of Quazepam. Pharmacodynamic effects were determined using visual analogue scales (VAS) and the digit symbol substitution test (DSST) on days 13 and 14. Results SJW decreased the plasma Quazepam concentration. The Cmax and AUC0-48 of Quazepam after SJW were significantly lower than those after placebo [Cmax; −8.7 ng ml−1 (95% confidence interval (CI) −17.1 to −0.2), AUC0-48; −55 ng h ml−1 (95% CI −96 to −15)]. The urinary ratio of 6β-hydroxycortisol to cortisol, which reflects CYP3A4 activity, also increased after dosing with SJW (ratio; 2.1 (95%CI 0.85–3.4)). Quazepam, but not SJW, produced sedative-like effects in the VAS test (drowsiness; P < 0.01, mental slowness; P < 0.01, calmness; P < 0.05, discontentment; P < 0.01). On the other hand, SJW, but not Quazepam impaired psychomotor performance in the DSST test. SJW did not influence the pharmacodynamic profile of Quazepam. Conclusions These results suggest that SJW decreases plasma Quazepam concentrations, probably by enhancing CYP3A4 activity, but does not influence the pharmacodynamic effects of the drug.
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Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam and Quazepam
Clinical Pharmacology & Therapeutics, 2004Co-Authors: Akio Fujimura, Masami Ohmori, Koichi Sugimoto, Shuichi Tsuruoka, N. Araki, Atsuhiro KawaguchiAbstract:Purpose The effects of grapefruit juice (GJ) on benzodiazepine hypnotics, triazolam (metabolized by CYP3A4) and Quazepam (metabolized by CYP3A4 and CYP2C) were determined in this study. Methods Nine healthy male subjects (genotyped as wild type CYP2C9) took triazolam 0.25mg or Quazepam 15mg with or without GJ. The trial was performed by a randomized, cross-over design with an interval of more than 2 weeks. Blood was obtained after each dosing. Phrmacodynamic effects were determined by digit symbol substitution test (DSST). Results GJ increased plasma concentrations of triazolam, and Quazepam and its active metabolite, 2-oxoQuazepam. The AUC of triazolam significantly increased by 96%. The elevations of this parameter of Quazepam (38%) and 2-oxoQuazepam (28%) were not significant. Triazolam reduced the number of digit substitutions while the effect of Quazepam on the DSST was negligible. GJ deteriorated the performance in the DSST at 2 h after dosing of triazolam (-11 digits, P
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interaction between grapefruit juice and hypnotic drugs comparison of triazolam and Quazepam
Clinical Pharmacology & Therapeutics, 2004Co-Authors: Akio Fujimura, Masami Ohmori, Koichi Sugimoto, Shuichi Tsuruoka, N. Araki, Y Cui, Atsuhiro KawaguchiAbstract:Purpose The effects of grapefruit juice (GJ) on benzodiazepine hypnotics, triazolam (metabolized by CYP3A4) and Quazepam (metabolized by CYP3A4 and CYP2C) were determined in this study. Methods Nine healthy male subjects (genotyped as wild type CYP2C9) took triazolam 0.25mg or Quazepam 15mg with or without GJ. The trial was performed by a randomized, cross-over design with an interval of more than 2 weeks. Blood was obtained after each dosing. Phrmacodynamic effects were determined by digit symbol substitution test (DSST). Results GJ increased plasma concentrations of triazolam, and Quazepam and its active metabolite, 2-oxoQuazepam. The AUC of triazolam significantly increased by 96%. The elevations of this parameter of Quazepam (38%) and 2-oxoQuazepam (28%) were not significant. Triazolam reduced the number of digit substitutions while the effect of Quazepam on the DSST was negligible. GJ deteriorated the performance in the DSST at 2 h after dosing of triazolam (-11 digits, P<0.05), but not of Quazepam. A significant correlation was observed between plasma triazolam concentration and the decrease in the number of digit substitutions at 2h after dosing (P<0.05). Conclusions These results suggest that the effects of GJ on the pharmacokinetics and pharmacodynamics of triazolam are greater than those of Quazepam. These GJ-related different effects are partly explained by the fact that triazolam is metabolized by CYP3A4, and Quazepam by CYP3A4 and CYP2C9. Clinical Pharmacology & Therapeutics (2004) 75, P29–P29; doi: 10.1016/j.clpt.2003.11.110
Toshiaki Aoshima - One of the best experts on this subject based on the ideXlab platform.
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single oral dose pharmacokinetics of Quazepam is influenced by cyp2c19 activity
Therapeutic Drug Monitoring, 2004Co-Authors: Takashi Fukasawa, Norio Yasuifurukori, Toshiaki Aoshima, Akihito Suzuki, Tomonori Tateishi, Koichi OtaniAbstract:The effects of cytochrome P450 (CYP)2C19 activity and cigarette smoking on the single oral dose pharmacokinetics of Quazepam were studied in 20 healthy Japanese volunteers. Twelve subjects were extensive metabolizers (EMs), and 8 subjects were poor metabolizers (PMs) by CYP2C19 as determined by the PCR-based genotyping. Nine subjects were smokers (>10 cigarettes/d), and 11 subjects were nonsmokers. The subjects received a single oral 20-mg dose of Quazepam, and blood samplings and evaluation of psychomotor function were conducted up to 72 hours after dosing. Plasma concentrations of Quazepam and its active metabolite 2-oxoQuazepam (OQ) were measured by HPLC. There were significant differences between EMs and PMs in the peak plasma concentration (mean +/- SD: 34.5 +/- 16.6 versus 66.2 +/- 19.2 ng/mL, P < 0.01) and total area under the plasma concentration-time curve (490.1 +/- 277.5 vs 812.1 +/- 267.2 ng x h/mL, P < 0.05) of Quazepam. The pharmacokinetic parameters of OQ and pharmacodynamic parameters were not different between the 2 groups. Smoking status did not affect the pharmacokinetic parameters of Quazepam and OQ or pharmacodynamic parameters. The present study suggests that the single oral dose pharmacokinetics of Quazepam are influenced by CYP2C19 activity but not by cigarette smoking.
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interaction study between fluvoxamine and Quazepam
The Journal of Clinical Pharmacology, 2003Co-Authors: Hideto Kanda, Norio Yasuifurukori, Takashi Fukasawa, Toshiaki Aoshima, Akihito Suzuki, Koichi OtaniAbstract:It has been reported that fluvoxamine, an inhibitor of various cytochrome P450 enzymes, markedly inhibits the metabolism of several drugs. The purpose of the present study was to examine a possible interaction between fluvoxamine and Quazepam. Twelve healthy male volunteers received fluvoxamine 50 mg/day or placebo for 14 days in a double-blind randomized crossover manner, and on the 4th day they received a single oral 20-mg dose of Quazepam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 240 hours after Quazepam dosing. Plasma concentrations of Quazepam and its active metabolites 2-oxoQuazepam (OQ) and N-desalkyl-2-oxoQuazepam (DOQ) were measured by high-performance liquid chromatography (HPLC). Fluvoxamine did not change plasma concentrations of Quazepam but significantly decreased those of OQ from 6 to 12 hours and those of DOQ from 3 to 48 hours. The AUC ratio of OQ to Quazepam was significantly lower in the fluvoxamine phase. Fluvoxamine did not affect psychomotor function at most of the time points. The present study suggests that fluvoxamine slightly inhibits the metabolism of Quazepam to OQ, but this interaction appears to have minimal clinical significance.
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effects of itraconazole on the plasma kinetics of Quazepam and its two active metabolites after a single oral dose of the drug
Therapeutic Drug Monitoring, 2003Co-Authors: Kimiyasu Kato, Norio Yasuifurukori, Takashi Fukasawa, Toshiaki Aoshima, Akihito Suzuki, Muneaki Kanno, Koichi OtaniAbstract:The effects of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the plasma kinetics of Quazepam and its two active metabolites after a single oral dose of the drug were studied. Ten healthy male volunteers received itraconazole 100 mg/d or placebo for 14 days in a double-blind randomized crossover manner, and on the fourth day of the treatment they received a single oral 20-mg dose of Quazepam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 240 h after Quazepam dosing. Itraconazole treatment did not change the plasma kinetics of Quazepam but significantly decreased the peak plasma concentration and area under the plasma concentration-time curve of 2-oxoQuazepam and N-desalkyl-2-oxoQuazepam. Itraconazole treatment did not affect either of the psychomotor function parameters. The present study thus suggests that CYP 3A4 is partly involved in the metabolism of Quazepam.
